共查询到20条相似文献,搜索用时 15 毫秒
1.
ShuangQuan Liu ShiPing Wang YiMou Wu FeiJun Zhao TieBing Zeng YueJun Zhang QiuGui Zhang DongMei Gao 《中国科学:生命科学英文版》2010,53(2):229-233
The tissue destruction characteristic of syphilis infection may be caused by inflammation due to Treponema pallidum and the ensuing immune responses to the pathogen. T. pallidum membrane proteins are thought to be potent inducers of inflammation during the early stages of infection. However, the actual
membrane proteins that induce inflammatory cytokine production are not known, nor are the molecular mechanisms responsible
for triggering and sustaining the inflammatory cascades. In the present study, Tp0751 recombinant protein from T. pallidum was found to induce the production of proinflammatory cytokines, including TNF-α, IL-1βand IL-6, in a THP-1 human monocyte
cell line. The signal transduction pathways involved in the production of these cytokines were then further investigated.
No inhibition of TNF-a, IL-1β, or IL-6 production was observed following treatment with the SAPK/JNK specific inhibitor SP600125
or with an ERK inhibitor PD98059. By contrast, anti-TLR2 mAb, anti-CD14 mAb, and the p38 inhibitor SB203580 significantly
inhibited the production of all three cytokines. In addition, pyrrolidine dithiocarbamate (PDTC), a specific inhibitor of
NF-κB, profoundly inhibited the production of these cytokines. Tp0751 treatment strongly activated NF-κB, as revealed by Western
blotting. However, NF-κB translocation was significantly inhibited by treatment with PDTC. These results indicated that TLR2,
CD14, MAPKs/p38, and NF-κB might be implicated in the inflammatory reaction caused by T. pallidum infection. 相似文献
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Parfenyuk S. B. Khrenov M. O. Novoselova T. V. Glushkova O. V. Lunin S. M. Fesenko E. E. Novoselova E. G. 《Biophysics》2010,55(2):317-323
Effects of three chemical compounds: ammonia, diethyl ether, and acetic acid, known as common environmental contaminants in
technogenic accidents, were investigated in vivo and in vitro in low concentrations. When added in cultivation media, each
of the chemicals has affected peritoneal macrophages and spleen lymphocytes isolated from male NMRI mice and led to a rise
in the production of several cytokines, particularly the tumor necrosis factor-α and interferon-γ, as well as the expression
of the inducible form of heat shock proteins (HSP72 and HSP90-α) and in the activation of signal cascades NF-κB and SAPK/JNK.
The increase of the nitric oxide (NO) production in macrophages has been observed only when ammonia was added in cultivation
media. Also, low concentrations of all compounds investigated led to the activation of the expression of receptor protein
TLR4. When mice were exposed to airborne toxic contaminants in a hermetically sealed experimental chamber, an increase in
the concentrations of cytokines, heat shock proteins, and signal proteins in immune cells was also observed in response to
low concentrations of all chemicals investigated. Similarly to in vitro experiments, the NO production was augmented only
in the presence of the airborne ammonia. The results indicate the environmental hazard of chemical contaminants even in rather
low concentrations, which nevertheless lead to the stress response. 相似文献
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Lang Bai Shanling Xu Wenshu Chen Zi Li Xia Wang Hong Tang Yong Lin 《Apoptosis : an international journal on programmed cell death》2011,16(1):45-54
NF-κB and Akt are two main cell survival pathways that attenuate the anticancer efficacy of therapeutics. Our previous studies
demonstrated that the Smac mimetic compound 3 (SMC3) specifically suppresses c-IAP1 and induces TNF-α autocrine to kill cancer
cells. However, SMC3 also induces a cell survival signal through NF-κB activation. In this report, we further found that SMC3
potently activates Akt, which inhibits SMC3-induced cancer cell death. Strikingly, concurrent blocking NF-κB and Akt resulted
in a significantly potentiated cytotoxicity. Because heat shock protein 90 (Hsp90) plays an important role in maintaining
the integrity of both the NF-κB and Akt pathways in cancer cells, we examined if suppression of Hsp90 is able to potentiate
SMC3-induced cancer cell death. The results show that targeting Hsp90 does not interfere with SMC3-induced c-IAP1 degradation
and TNF-α autocrine, the key processes for SMC3-induced cancer cell apoptosis. However, Hsp90 inhibitors effectively blocked
SMC3-induced NF-κB activation through degradation of RIP1 and IKKβ, two key components of the NF-κB activation pathway, and
reduced both the constitutive and SMC3-induced Akt activity through degradation of the Akt protein. Consistently, with the
co-treatment of SMC3 and Hsp90 inhibitors, apoptosis was markedly sensitized and a synergistic cytotoxicity was observed.
The results suggest that concurrent targeting c-IAP1 and Hsp90 by combination of SMC3 and Hsp90 inhibitors is an effective
approach for improving the anticancer value of SMC3. 相似文献
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T. V. Novoselova O. V. Glushkova S. B. Parfenuyk M. O. Khrenov S. M. Lunin T. I. Smolikhina E. E. Fesenko E. G. Novoselova 《Biophysics》2014,59(1):86-90
In vitro and in vivo effects of some inhibitors of the activity of signal cascades NF-κB and SAPK/JNK, and the TLR4 receptor on the immune cells activity were studied. To evaluate in vitro effects, the macrophage-like RAW 264.7 cells were cultured with each of the inhibitors, namely IKK inhibitor XII, SP600125, CLI-095, and OxPAPK (the first two are the inhibitors of NF-κB, SAPK/JNK cascades, and the last two compounds are the inhibitors of the TLR4 receptor activity). On the whole, all of the used inhibitors did not induce pro-inflammatory response in RAW 264.7 cells. On the contrary, the inhibitor of SAPK/JNK cascade, and, especially, the inhibitor of NF-κB cascade significantly decreased production of the TNF-α, IL-1, IL-6, IFN-γ, and IL-10 in RAW 264.7 cells. In these cells, the inhibitors substantially decreased “back-ground stress response” of macrophages, differently reducing a production of heat shock proteins, HSP72 and HSP90-α, and diminishing phosphorylation of signal proteins from NF-κB and SAPK/JNK cascades. Results of in vitro experiments suggest that the inhibitor of NF-κB activity was the most effective. It was this inhibitor that was intraperitonealy injected in Balb/C male mice in the in vivo experiments in order to study its effect on the activity of immune cells. Results showed that IKK Inhibitor XII applied in vivo did not induce pro-inflammatory response in mice, but decreased the activity of NF-κB cascade, and lowered HSP90-α expression in mouse splenic lymphocytes. So, among the studied compounds, IKK Inhibitor XII seems to be a very effective inhibitor that may be used to decrease cytokine and stress response in various pathologies. 相似文献
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Salsolinol, an endogenous neurotoxin, is known to be involved in the pathogenesis of Parkinson’s disease (PD). In the present
study, we have investigated the effects of salsolinol on the activation of two different signaling pathways that involve c-Jun
N-terminal kinase (JNK), and nuclear factor-κB, (NF-κB) in human dopaminergic neuroblastoma SH-SY5Y cells. Salsolinol treatment
caused upregulation in the levels of c-Jun and phosphorylated c-Jun. It also caused degradation of IκBα and translocated the
active NF-κB into the nucleus. The binding activity of NF-κB to DNA was enhanced by salsolinol in a concentration dependent
manner. Furthermore, salsolinol decreased the levels of the anti-apoptotic protein Bcl-2, and increased pro-apoptotic protein
Bax, while enhancing the release of cytochrome-c from mitochondria. Mitochondrial complex-I activity was significantly decreased and reactive oxygen species (ROS) were increased
in salsolinol treated cells. These results partly suggest that salsolinol-induced JNK and NF-κB signaling pathways may be
involved in induction of apoptosis in human dopaminergic neurons, as seen in Parkinson’s disease. 相似文献
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D. A. Cherenkov E. G. Novoselova M. O. Khrenov O. V. Glushkova S. M. Lunin T. V. Novoselova E. E. Fesenko 《Biophysics》2009,54(2):179-181
The effect of low-intensity laser light (He-Ne, 0.2 mW/cm2, 632.8 nm, exposure time 1 min) or centimeter waves (8.15–18 GHz, 1 μW/cm2, exposure time 1 h) on Phospho-SAPK/JNK production in mice lymphocytes was investigated. Normal isolated spleen lymphocytes or cells incubated previously with geldanamycin, an inhibitor of Hsp90, were used in the experiments. Significant stimulation of Phospho-SAPK/JNK production in lymphocytes after treatment with laser light or microwaves has been shown in both cell models. It was proposed that activation of the SAPK/JNK signal pathway plays one of the central roles in cellular stress response to low-power nonionizing radiation. 相似文献
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Ellen M Gravallese Deborah L Galson Steven R Goldring Philip E Auron 《Arthritis research & therapy》2000,3(1):6-7
The contribution of osteoclasts to the process of bone loss in inflammatory arthritis has recently been demonstrated. Studies in osteoclast biology have led to the identification of factors responsible for the differentiation and activation of osteoclasts, the most important of which is the receptor activator of NF-κB ligand/osteoclast differentiation factor (RANKL/ODF), a tumor necrosis factor (TNF)-like protein. The RANKL/ODF receptor, receptor activator of NF-κB (RANK), is a TNF-receptor family member present on both osteoclast precursors and mature osteoclasts. Like other TNF-family receptors and the IL-1 receptor, RANK mediates its signal transduction via TNF receptor-associated factor (TRAF) proteins, suggesting that the signaling pathways activated by RANK and other inflammatory cytokines involved in osteoclast differentiation and activation are interconnected. 相似文献
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Amrie C Grammer Randy Fischer Olivia Lee Xuan Zhang Peter E Lipsky 《Arthritis research & therapy》2003,6(1):28
Abnormalities in lymphocyte signaling cascades are thought to play an important role in the development of autoimmune disease.
However, the large amount of cellular material needed for standard biochemical assessment of signaling status has made it
difficult to evaluate putative abnormalities completely using primary lymphocytes. The development of technology to employ
intracellular staining and flow cytometry to assess the signaling status of individual cells has now made it possible to delineate
the perturbations that are present in lymphocytes from patients with autoimmune disease. As an example, human B cells from
the Ramos B cell line and the periphery of systemic lupus erythematosus (SLE) patients or normal nonautoimmune controls were
assessed for activation of the NF-κB and mitogen activated protein kinase (MAPK) signaling cascades by intracellular multiparameter
flow cytometric analysis and biochemical Western blotting. In combination with fluorochrome conjugated antibodies specific
for surface proteins that define B cell subsets, antibodies that recognize activated, or phosphorylated inhibitors of κB (IκB)
as well as the extracellular regulated kinase (ERK), jun N-terminal kinase (JNK) or p38 MAPKs were used to stain fixed and
permeabilized human B cells and analyze them flow cytometrically. Examination of the known signaling pathways following engagement
of CD40 on human B cells confirmed that intracellular flow cytometry and Western blotting equivalently assay CD154-induced
phosphorylation and degradation of IκB proteins as well as phosphorylation of the MAPKs ERK, JNK and p38. In addition, B cells
from the periphery of SLE patients had a more activated status immediately ex vivo as assessed by intracellular flow cytometric analysis of phosphorylated ERK, JNK and p38 when compared with B cells from
the periphery of normal, nonautoimmune individuals. Together, these results indicate that multiparameter intracellular flow
cytometric analysis of signaling pathways, such as the NF-κB and MAPK cascades, can be used routinely to assess the activation
status of a small number of cells and thus delineate abnormalities in signaling molecules expressed in primary lymphocytes
from patients with autoimmune disease. 相似文献
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Jung Ha Kim Kabsun Kim Hye Mi Jin Insun Song Bang Ung Youn Junwon Lee Nacksung Kim 《Molecules and cells》2009,28(3):201-207
Silibinin is a polyphenolic flavonoid compound isolated from milk thistle (Silybum marianum), with known hepatoprotective, anticarcinogenic, and antioxidant effects. Herein, we show that silibinin inhibits receptor
activator of NF-κB ligand (RANKL)-induced osteoclastogenesis from RAW264.7 cells as well as from bone marrow-derived monocyte/macrophage
cells in a dose-dependent manner. Silibinin has no effect on the expression of RANKL or the soluble RANKL decoy receptor osteoprotegerin
(OPG) in osteoblasts. However, we demonstrate that silibinin can block the activation of NF-κB, c-Jun N-terminal kinase (JNK),
p38 mitogen-activated protein (MAP) kinase, and extracellular signal-regulated kinase (ERK) in osteoclast precursors in response
to RANKL. Furthermore, silibinin attenuates the induction of nuclear factor of activated T cells (NFAT) c1 and osteoclast-associated
receptor (OSCAR) expression during RANKL-induced osteoclastogenesis. We demonstrate that silibinin can inhibit TNF-α-induced
osteoclastogenesis as well as the expression of NFATc1 and OSCAR. Taken together, our results indicate that silibinin has
the potential to inhibit osteoclast formation by attenuating the downstream signaling cascades associated with RANKL and TNF-α. 相似文献
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